Bimatoprost is the generic name of compound (Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxy-5-phenylpent-1-enyl]cyclopentyl]-N-ethylhept-5-enamide, the chemical structure of which is the following:

Bimatoprost is a prostaglandin derivative of the PGF2α-series used topically (as eye drops) to control the progression of glaucoma and in the management of ocular hypertension.
Bimatoprost was first disclosed in document WO199406433. This document, as well as later documents such as WO2002096868 and WO20100109476, discloses processes for the preparation of bimatoprost wherein in the last step of the synthesis the amide moiety is formed via a methyl ester intermediate by reaction with ethylamine. The methyl ester intermediate is previously obtained by reaction of the corresponding carboxylic acid with IMe. The reaction is carried out either with the hydroxyl groups of the molecule unprotected or protected in part. The use of IMe is not advisable as it is considered to be a human carcinogen. Additionally, the reaction of the methyl ester with ethylamine to obtain the ethylamide derivative takes place at a very low speed and with the formation of the corresponding carboxylic acid as side-product in a significant amount.
WO2005058812 discloses a process for the preparation of bimatoprost from a tripotected precursor having a free carboxylic acid group. The amidation reaction is carried out either with ethylamine in the presence of a carbodiimide or with previous esterification (formation of the methyl ester as mentioned above) of the corresponding acid precursor. Nevertheless, overall yields reported are very low.
A variety of methods synthesising bimatoprost or other PGFα prostaglandins analogues have been disclosed following several alternatives. In general, the ones wherein the α-chain is introduced using the Wittig reagent 4-(carboxybutyl)triphenylphosphonium bromide to give the corresponding acid which has to be converted into an amide to obtain bimatoprost require the use of elaborated protecting group strategies. As an alternative to the formation of an ester previously to the amidation reaction, the acid is activated by groups other than an ester. Nevertheless, these alternative processes require the use of reactants that either are toxic or generate toxic waste, what is a drawback for the production on an industrial scale. Additionally, bimatoprost is obtained in insufficient purity.
In view of the processes disclosed in the prior art, particularly the ones disclosed herein above, and the problems associated therewith, it is an object of the present invention to provide an alternative process for the synthesis of bimatoprost.